Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease

Abstract

Inflammatory Bowel Diseases (IBD) are chronic conditions characterized by inflammation of the gastrointestinal tract that heavily burden daily life, result in surgery or other complications, and disrupt the gut microbiome. How IBD influences gut microbial ecology, especially biogeographic patterns of microbial location, and how the gut microbiota can use diet components and microbial metabolites to mediate disease, are still poorly understood. Many studies on diet and IBD in mice use a chemically induced ulcerative colitis model, despite the availability of an immune-modulated Crohn's Disease model. Interleukin-10-knockout (IL-10-ko) mice on a C57BL/6 background, beginning at age 4 or 7 weeks, were fed either a control diet or one containing 10% (w/w) raw broccoli sprouts which was high in the sprout-sourced anti-inflammatory sulforaphane. Diets began 7 days prior to inoculation with Helicobacter hepaticus, which triggers Crohn's-like symptoms in these immune-impaired mice, and ran for two additional weeks. Key findings of this study suggest that the broccoli sprout diet increases sulforaphane concentration in plasma; decreases weight stagnation, fecal blood, and diarrhea associated with enterocolitis; and increases microbiota richness in the gut, especially in younger mice. Sprout diets resulted in some anatomically specific bacterial communities in younger mice, and reduced the prevalence and abundance of potentially pathogenic or otherwise-commensal bacteria which trigger inflammation in the IL-10 deficient mouse, for example, Escherichia coli and Helicobacter. Overall, the IL-10-ko mouse model is responsive to a raw broccoli sprout diet and represents an opportunity for more diet-host-microbiome research. A diet containing 10% raw broccoli sprouts increased the plasma concentration of the anti-inflammatory compound sulforaphane, and may be protective against negative disease characteristics of Helicobacter-induced enterocolitis in interleukin-10 knockout mice, including weight loss or stagnation, fecal blood, and diarrhea. Younger mice responded more strongly to the diet intervention, and resulted in increased gut bacterial community richness and bacterial community similarity by diet treatment and some anatomical locations in the gut, even in mice with adverse reactions to gut microbiota and a relatively short time in which they had been able to recruit them. To our knowledge, IL-10-ko mice have not previously been used to investigate the interactions of host, microbiota, and broccoli, broccoli sprouts, or broccoli bioactives in resolving symptoms of CD.

Current Knowledge on the Preparation and Benefits of Cruciferous Vegetables as Relates to In Vitro, In Vivo, and Clinical Models of Inflammatory Bowel Disease

“…Similar to the findings from in vitro studies, broccoli has been reported to have anti-inflammatory, antioxidant, and prebiotic effects against IBD in animal models ( Table 2 [ 48 , 99 , 102 , 105 , 107 , 111 , 112 , 116 , 118 , 122 , 125 , [127] , [128] , [129] , [130] , [131] , [132] , [133] , [134] , [135] , [136] , [137] , [138] , [139] , [140] , [141] ] and Figure 1 ). Both the UC and CD models use chemical triggers or genetic knockouts.…”

“… Prebiotic, Anti-inflammatory mdr1a−/− mice [ 132 ] SFN Crude extract 4% 12 d NFkB, TNFɑ, IL10, MCP-1, and COX 2 No significance DSS-rat [ 102 ] N.R. Juice 1.5 mL 7 d IL8 Anti-inflammatory DSS mice [ 133 ] SFN, Lipids Edible nanoparticles mean diameter 32.4 nm 10 and 13 d AMPK, IL10, TNFɑ, IL17A and IFN-γ Anti-inflammatory DSS mice [ 116 ] SFN, Lipids Edible nanoparticles mean diameter 32.4 nm 10 d TNFɑ, IL6, and IL23 Anti-inflammatory Rag1−/− mice [ 116 ] Broccoli sprouts GLR, SFN Steamed and freeze-dried 10% (w/w) 34 d Bacillota, Pseudomonadota, Bacteroidota and Verrucomicrobiota; TNFɑ, IL1β and IL6 Prebiotic, Anti-inflammatory DSS mice [ 48 ] SFN, GLR Streamed 5% (w/w) 13 d microbial hydrolase, Bacillota Prebiotic DSS mice [ 105 ] SFN raw 10% (w/w) 2 wk E. coli and Helicobacter Prebiotic, Anti-inflammatory IL10-KO mice [ 134 ] Broccoli sprouts and seed GLR, Glucoiberin, Glucoerucin,...…”

“…The study used IL10-knockout mice as a CD model and found higher serum SFN and microbial diversity in young mice than in adult mice. The diet decreased IBD symptoms, such as diarrhea, fecal blood, and pathobiont bacteria such as E. coli and Helicobacter, to alleviate dysbiosis and inflammation [ 134 ].…”

Research advancements and perspectives of inflammatory bowel disease: A comprehensive review

“…Many dietary contents have protective potential in IBD treatments, such as Spermidine, Chlorophyllin in green vegetables, steamed or raw broccoli sprouts with high levels of sulforaphane and fruits like avocado. 54 – 59 Spermidine, with high levels in soybeans, wheat germ, and aged cheese, has strong anti-inflammatory potential via promoting an M2-like macrophage differentiation, while it is ineffective in the macrophages of IBD patients carrying PTPN2 SNP rs1893217. 54 Mannose, exerts a potential therapeutic effect on both DSS-induced and IL-10-deficient colitis mouse models by limiting cathepsin B release from lysosomes which prevents mitochondrial dysfunction and TJs disruption.…”

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“…As a result, it exhibits progressive development of chronic enteritis without intervention, contrasting with the chemical-induced IBD model in healthy animals. Additionally, the modeling cycle for this model is notably longer than the included model (Singh et al, 2012;Holcomb et al, 2023). OVA primarily induces allergic enteritis, predominantly mediated by type I hypersensitivity through IgE (Kato et al, 2023).…”